Supplementary material

Molecular modeling studies of 1,2,4-triazine derivatives as novel h-DAAO

inhibitors by 3D-QSAR, docking and dynamics simulationsPing Ping Qian, Shuai Wang, Kai Rui Feng and Yu Jie Ren**School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China

E-mail: clab@sit.edu.cn

Table 1S Uni-column statistics of the training and test sets for the 3D-QSAR model studyData set Inhibitory potency Average Maximum Minimum Standard Deviation SumTraining pIC50 6.717 7.398 4.000 0.704 208.236

Test pIC50 6.153 7.301 4.398 1.138 36.917

Fig. 1S Histogram of biological data distribution statistics in the 3D-QSAR analysis

Electronic Supplementary Material (ESI) for RSC Advances.This journal is © The Royal Society of Chemistry 2018

Fig. 2S Efficient color histogram indexing for the q2 values of probable field combinations in CoMSIA analysis. (green: combinations with higher q2 values, red: the best field combination).

Fig. 3S Basic flowchart of research programme.

Fig. 4S Docking results of all compounds and surface of the binding site. (yellow lines: hydrogen bonds)

Fig. 5S The binding pocket (a), docking results and surface of compound 4 (b), 5 (c) and 6 (d). (blue lines: hydrogen bonds)

Fig. 6S Docking results of all designed compounds into the binding site of protein 3W4K. (yellow lines: hydrogen bonds)

Fig. 7S The total-energy (a) and temperature (b) of the inhibitor-protein complexes versus dynamics time.

Fig. 8S Structural comparison between original structure (purple) and dynamics equilibrium structure (green) of 13-3W4K.

Fig. 9S Root-mean-square fluctuation (RMSF) the ligand-3W4K complexes versus residue number. (a: Tyr224; b: Tyr228; c: Arg283; d: Gly313)

Fig. 10S The bioavailability radars for compounds 13 (a), D1 (b), D3 (c) and D8 (d).

Fig. 11S The BOILED-Egg model for intuitive assessment of HIV and BBB through the position of the representative compounds.